胶乳增强免疫比浊法测定人血浆多西他赛浓度方法学评价及其临床应用

目的：对胶乳增强免疫比浊法测定人血浆多西他赛浓度方法学进行评价。方法：测定10例乳腺癌患者血浆多西他赛的浓度，应用NCCLS标准化评价方案分析测定方法的精密度、线性范围、回收率和抗干扰试验等。结果：多西他赛低、中、高3个浓度批内变异系数分别为3.4%，1.5%，1.0%；批间变异系数分别为5.5%，2.4%，1.8%；平均回收率为100.49%。检测线性范围为75~1 000 ng·mL^-1。分别用UPLC-MS/MS法和胶乳免疫比浊法进行比对，线性回归方程为y=0.978x-1.18，相关系数r=0.998 0，两者差异无显著性（P>0.05），两方法存在良好相关性。与多西他赛联合使用的药物，如奥沙利铂、阿霉素等，药物质量浓度为100 mg·mL^-1时，交叉反应率≤0.1%。类风湿因子≤1 200 IU·L^-1，胆红素≤146 mg·dL^-1，血红蛋白≤7.5 g·L^-1，三酰甘油≤3 185 mg·dL^-1时对测定结果没有干扰。结论：胶乳免疫比浊法测定人血浆多西他赛浓度简便、快速、准确，适用于多西他赛的临床治疗药物浓度监测。

Evaluation of latex-enhanced turbidimetric immunoassay for determining docetaxel concentrations and its clinical application

OBJECTIVE To preliminarily evaluate the latex-enhanced turbidimetric immunoassay (IETIA) in determination of docetaxel in human plasma. METHODS The accuracy, precision, linearity, recovery and anti-interference of IETIA were analyzed in accordance with the National Committee for Clinical Laboratory Standards (NCCLS) through determination of docetaxel in 10 breast cancer patients. RESULTS The intra-day coefficients of variation (CVs) of docetaxel were 3.4% (low value), 1.5% (medium value) and 1.0% (high value), respectively, while the inter-day CVs were 5.5% (low value), 2.4% (medium value) and 1.8% (high value), and the recovery was 100.49%. The standard curve of docetaxel was linear in concentration range of 75-1 000 ng·mL^-1. Method comparison results between IETIA and UPLC-MS/MS were performed using 92 human plasma samples obtained from patients received docetaxel therapy, demonstrating a slope=0.978, intercept=-1.18 and an r=0.998 0, showing good correlation. Compounds combining with DTX cross-reacted≤0.1% in the assay when the drug concentration was 100 mg·mL^-1. The interference test showed that the RSD of the method was less than 5% when the rheumatoid factor was less than 1 200 IU·L^-1, hemoglobin level was lower than 146 mg·dL^-1, total bilirubin level was lower than 7.5 g·L^-1 and triglyceride concentration was lower than 3 185 mg·dL^-1. CONCLUSION This method is proved to be simple, sensitive, rapid and accurate for determination of docetaxel in clinical therapeutic drug monitoring.